In the pieces on this page, there is much talk about mystical, spiritual experiences. A question many people ask is, "What's a mystical experience?" Indeed, if there are sacred sacraments that can make mystical religious experiences available to most people who would otherwise not know what those words refer to, then most of you who have not tried the sacraments may not know what we are talking about! This poses a serious problem because it is not OK to just say,

"Well, you haven't had THE experience, so you don't know what we are talking about. You don't know what our evidence is, so you can't question our conclusions."

Such claims are commonly made to insulate true believers of many stripes from any critical thinking about their beliefs.

In response to this problem, we have provided The Yo FAQ and The Word, According to Yo, which explain what is meant by mystical experience and then we attempt to ground the concepts (what our "mystical" words are referring to) in modern science. You may have to struggle to understand what we are saying in The FAQ and The Word; the conclusions—which, after all, are "mystical," i.e., they transcend ordinary reality and turn some notions inside out—will challenge your typical views of existence. Ordinary waking reality is just "the tip of the iceberg." The Truth is strange, indeed.

You may need to install or update your Adobe Flash Player to view many of the videos on this site.

Drugs and God?

BTW, Harvard University maintains an archive of the the work of R. Gordon Wasson, the ethnomycologist whose research showed that "entheogenic" (a word that Wasson coined) mushrooms played an important role in the history of human religion. Wasson "discovered" (for Western science, that is) magic mushrooms back around 1953, when early reports weren't automatically enshrouded in drug war propaganda.

Go Ask Alice:
Mushroom Drug
Is Studied Anew

By
RON WINSLOW
July 11, 2006; Page B1

In a study that could revive interest in researching the
effects of psychedelic drugs, scientists said a substance in certain
mushrooms induced powerful, mind-altering experiences among a group of
well-educated, middle-age men and women.

Johns Hopkins Medical Institutions researchers conducted
the study following carefully controlled, scientifically rigorous
procedures. They said that the episodes generally led to positive changes in
attitude and behavior among the 36 volunteer participants and that the
changes appeared to last at least two months. [Note: Follow up research showed that the positive effects lasted more than a year.] Participants cited feelings of
intense joy, "distance from ordinary reality," and feelings of peace and
harmony after taking the drug. Two-thirds described the effects of the drug,
called psilocybin, as among the five most meaningful experiences of their
lives.

But in 30% of the cases, the drug provoked harrowing
experiences dominated by fear and paranoia. Two participants likened the
episodes to being in a war. While these episodes were managed by trained
monitors at the sessions where the drugs were taken, researchers cautioned
that in less-controlled settings, such responses could trigger panic or
other reactions that might put people in danger.

A report on the study, among the first to systematically
assess the effects of hallucinogenic substances in 40 years, is being
published online today by the journal Psychopharmacology. An accompanying
editorial and commentaries from three prominent neuroscientists and a
psychiatrist praise the study and argue that further research into such
agents has the potential to unlock secrets of consciousness and lead to new
therapeutic strategies for depression, addiction and other ailments.

In one of the commentaries, Charles R. Schuster, a
neuroscientist and former head of the National Institute for Drug Abuse,
called the report a "landmark paper." He also expressed hope that it "renews
interest in a fascinating and potentially useful class of psychotropic
agents."

Still, the research is likely to stir controversy. Though
psilocybin mushrooms, which can be found growing wild throughout the world,
have been used for centuries in some societies during spiritual rituals,
they also were agents, along with such hallucinogens as LSD and mescaline,
that fueled the "Turn On, Tune In, Drop Out" counterculture of the 1960s
personified by Timothy Leary.

Researchers acknowledge that the study's positive findings
may encourage inappropriate use of the agents. Roland Griffiths, the Hopkins
neuroscientist who headed the research, warned against viewing the results
as a green light for consuming the mushrooms. "We don't know all their dark
sides," he said. "I wouldn't in any way want to underestimate the potential
risks" of indiscriminate use of the drugs.

The National Institute for Drug Abuse, which co-sponsored
the study as part of its support for research into drugs of abuse, also
warned against eating psilocybin mushrooms. They "act on serotonin receptors
in the brain to profoundly distort a person's perception of reality," the
institute said, possibly triggering psychosis, paranoia and anxiety.

It was widespread abuse in the 1960s that led to
hallucinogens becoming illegal, effectively shutting down then-burgeoning
corporate and academic research programs that had suggested the agents might
be valuable research and therapeutic tools. One of the last influential
studies was the Good Friday Experiment in 1962 in which 20 seminary students
were given either psilocybin or nicotinic acid during a religious service.
The 10 who got psilocybin reported intense spiritual experiences with
positive benefits; one follow-up study suggested those effects lasted 25
years.

"It's remarkable that we have a class of compounds that has
sat in the deep freeze for 40 years," Dr. Griffiths said. "It seemed to me
scientifically it was high time to look again" at psychedelic agents.

Known colloquially by such names as magic mushroom or
sacred mushroom, psilocybin is considered a Schedule I substance under the
U.S. Controlled Substances Act. That puts it in the same class as heroin and
LSD, drugs that have a high potential for abuse and no known medical use. It
isn't considered addictive. The psilocybin used in the study was synthesized
by David E. Nichols, a professor of medicinal chemistry at Purdue
University, West Lafayette, Ind., under a special permit.

After getting approval from the Drug Enforcement
Administration, the Food and Drug Administration and an institutional review
board at Hopkins, Dr. Griffiths and his colleagues circulated a flier
seeking volunteers for a "study of states of consciousness brought about by
a naturally occurring psychoactive substance used sacramentally in some
cultures."

From among the 135 people who responded, 36 were eventually
selected, based in part on their lack of a history of psychedelic drug use
or family history of serious psychiatric disorders such as schizophrenia.
The 36 -- 14 men and 22 women -- ranged in age from 24 to 64 years old, with
an average age of 46; 97% were college graduates, and 56% had post-graduate
degrees. All 36 participated at least occasionally in religious or spiritual
activities. (Dr. Griffiths declined to make any participants available for
interviews, citing privacy issues.)

Thirty of the participants were randomly assigned to
receive either psilocybin or Ritalin (known generically as methylphenidate)
as a control for the first eight-hour session; two months later, they were
given the other drug in another session. Neither the participants nor the
monitors who were present during their sessions knew which agent was being
taken. To further reduce chances that participant responses would be
affected by expectations they were getting psilocybin, a third group of six
participants was randomly assigned to receive Ritalin in both sessions,
followed by a third session when they knew they were getting the psychedelic
agent. Ritalin was selected as the control agent in part because it can
cause mood-changing effects similar to those of psilocybin, researchers
said. It also takes effect at about the same time and lasts for about as
long.

Participants were given the drug in individual sessions in
a living-room environment with two experienced monitors. They were
blindfolded, given headphones to listen to classical music and encouraged to
lie down and direct their thoughts inward.

Researchers provided participants with a battery of
questionnaires and mysticism scales, some of which were developed based on
research from more than four decades ago, to measure their impressions of
their experience at the end of the session and again two months later.

A third of the participants said the experience with
psilocybin was the single most significant experience of their lives, and an
additional 38% rated it among their top five such experiences -- akin to,
say, the birth of a first child or the death of a parent. Just 8% of the
Ritalin episodes were reported to be among the top five meaningful
occurrences. Two months after the sessions, 79% of the participants
indicated in questionnaires that their sense of well-being and satisfaction
increased after the psilocybin episodes, compared with 21% for Ritalin.

Researchers hope the findings will spur other studies that
will, for instance, compare the effects of other hallucinogens and use MRIs
to observe how such drugs affect the human brain. Other efforts are expected
to test the value of psilocybin as a therapy. Charles Grob, a researcher at
UCLA, is heading a small study to see if the drug relieves anxiety,
depression and pain among patients with advanced cancer. [That study's results are described here.]

Dr. Griffiths said another goal is to understand the
consequences of spiritual experiences -- both drug-induced and spontaneous
-- and to determine how long they last and whether they lead to personality
changes.

Drug's Mystical Properties Confirmed36 Area Adults Took Psilocybin in Study; Many Called Experience Spiritual

By David BrownWashington Post Staff WriterTuesday, July 11, 2006; A08

Psilocybin, the active ingredient of "magic mushrooms," expands the mind. After a thousand years of use, that's now scientifically official.

The chemical promoted a mystical experience in two-thirds of people who took it for the first time, according to a new study. One-third rated a session with psilocybin as the "single most spiritually significant" experience of their lives. Another third put it in the top five.

The study, published online today in the journal Psychopharmacology, is the first randomized, controlled trial of a substance used for centuries in Mexico and Central America to produce mystical insights. Almost no research on a psychedelic drug in human subjects has been done in this country since the 1960s. It confirms what both shamans and hippies have long said -- taking psilocybin is a scary, reality-bending and occasionally life-changing experience.

The researchers say they hope the experiment opens a door to the study of a class of compounds that alter human perception and erode the boundaries of self -- at least in some users. They hope it will provide new insight into how the brain works and what neurochemical events underlie moments of mystical rapture.

If the generally positive effects of the drug are confirmed by other studies, the research is likely to raise the question of whether people should be allowed access to psilocybin for self-improvement or recreation.

Rigorous study of these substances has been shunned since the 1960s, although it is not legally prohibited. Research on them was a casualty of the muddled mix of science and advocacy by people like Timothy Leary, the LSD guru and former Harvard psychologist once called the "most dangerous man in America" by President Richard M. Nixon.

"Our study has shown we can conduct a study of this type safely, and that the effects produced are really quite interesting," said Roland R. Griffiths of Johns Hopkins University School of Medicine, who ran the experiment. "There is a clear neuroscience agenda to understand those effects, and clear clinical applications that could be pursued."

Other brain researchers hailed the experiment as much for the fact that it was done at all as for its findings.

"These are some of the most potent compounds we know of that can change consciousness," said David E. Nichols, a professor of medicinal chemistry at Purdue University who has studied the effects of psychedelics on rats and cultured cells. "It's kind of peculiar they have just been kind of sitting on the shelf for 40 years. There is no other class of biologically active substances I am aware of that have been ignored like that."

The study, which involved 36 middle-aged adults from the Baltimore-Washington area, was conducted over five years. The subjects were chosen from 135 people who answered newspaper ads. All said they were members of a religious organization, practiced meditation or took part in other spiritual activity.

The study was designed to minimize the effects of anticipation and group enthusiasm, which might color a person's response. It also sought to examine the delayed, as well as immediate, effects of the drug.

The volunteers were randomly assigned to take either 30 milligrams of psilocybin (chemically synthesized, not extracted from mushrooms) or 40 milligrams of methylphenidate, the stimulant sold as Ritalin. The sessions lasted eight hours in a room where a person could listen to music, relax on a couch with eyeshades or talk with two monitors always in attendance. Each subject then took the other drug in a different session two months later.

Of the 36 people, 22 had a "complete" mystical experience as judged by several question-based scales used for rating such experiences. Two-thirds judged it to be among their top five life experiences, equal to the birth of a first child or death of a parent. Two months after a session, the people who had taken psilocybin reported small but significant positive changes in behavior and attitudes compared with those who had taken Ritalin.

One-third of the subjects, however, said they experienced "strong or extreme" fear at some point in the hours after they took the hallucinogen. Four people said the entire session was dominated by anxiety or psychological struggle.

Nichols thinks that last finding should give people pause.

"I think these drugs are potentially very dangerous," he said. "I would be very disappointed if in any sense these results were used to encourage recreational use of these compounds. I wouldn't want to take responsibility for anyone under unmonitored conditions coming up with those feelings."

Alan Leshner, who headed the National Institute on Drug Abuse for seven years and now leads the American Association for the Advancement of Science, was both wary and excited about psilocybin's reported effects.

"If it is ultimately shown to be benign but enriches people's lives, who could object to that? But I don't have that level of confidence at this point, given the paucity of research on it," he said.

A scholar of mysticism, G. William Barnard of Southern Methodist University, suspects that most mystical traditions would not object to the idea that a chemical could allow a person to tune into a preexisting state of consciousness, usually ignored, just as fasting, prayer, yoga and other activities can. But there is less enthusiasm for the idea that this kind of research will unlock the mechanism of mystical insight.

"Most people I suspect would say that the neurochemistry is not the full cause of these experiences," he said.

When you take away the silly plot theme of The Matrix (that machines are using humans as Duracell batteries), you can find some great mystical messages. Reality is a construct in human minds that is structured by the universal field of matter/time/space (whatever that is made of). This universal field could be called Yo, The Divine Mystery. Or, as in this film clip, it could be called the Matrix.

Mushroom Drug Produces Mystical Experience

By THE ASSOCIATED PRESS

Filed at 12:31 a.m. ET

NEW YORK (AP) -- People who took an illegal drug made from mushrooms reported profound mystical experiences that led to behavior changes lasting for weeks -- all part of an experiment that recalls the psychedelic '60s.

Many of the 36 volunteers rated their reaction to a single dose of the drug, called psilocybin, as one of the most meaningful or spiritually significant experiences of their lives. Some compared it to the birth of a child or the death of a parent.

Such comments ''just seemed unbelievable,'' said Roland Griffiths of the Johns Hopkins University School of Medicine in Baltimore, the study's lead author.

But don't try this at home, he warned. ''Absolutely don't.''

Almost a third of the research participants found the drug experience frightening even in the very controlled setting. That suggests people experimenting with the illicit drug on their own could be harmed, Griffiths said.

Viewed by some as a landmark, the study is one of the few rigorous looks in the past 40 years at a hallucinogen's effects. The researchers suggest the drug someday may help drug addicts kick their habit or aid terminally ill patients struggling with anxiety and depression.

It may also provide a way to study what happens in the brain during intense spiritual experiences, the scientists said.

Funded in part by the federal government, the research was published online Tuesday by the journal Psychopharmacology.

Psilocybin has been used for centuries in religious practices, and its ability to produce a mystical experience is no surprise. But the new work demonstrates it more clearly than before, Griffiths said.

Even two months after taking the drug, pronounced SILL-oh-SY-bin, most of the volunteers said the experience had changed them in beneficial ways, such as making them more compassionate, loving, optimistic and patient. Family members and friends said they noticed a difference, too. [Note: Follow up research showed that the positive effects lasted more than a year.]

Time Lapse of Sacred Psilocybe Cubensis

Charles Schuster, a professor of psychiatry and behavioral neuroscience at Wayne State University and a former director of the National Institute on Drug Abuse, called the work a landmark.

''I believe this is one of the most rigorously well-controlled studies ever done'' to evaluate psilocybin or similar substances for their potential to increase self-awareness and a sense of spirituality, he said. He did not participate in the research.

Psilocybin, like LSD or mescaline, is one of a class of drugs called hallucinogens or psychedelics. While they have been studied by scientists in the past, research was largely shut down after widespread recreational abuse of the drugs during the 1960s, Griffiths said. Some work resumed in the 1990s.

''We've lost 40 years of (potential) research experience with this whole class of compounds,'' he said. Now, with modern-day scientific methods, ''I think it's time to pick up this research field.''

The study volunteers had an average age of 46, had never used hallucinogens, and participated to some degree in religious or spiritual activities like prayer, meditation, discussion groups or religious services. Each tried psilocybin during one visit to the lab and the stimulant methylphenidate (better known as Ritalin) on one or two other visits. Only six of the volunteers knew when they were getting psilocybin.

Each visit lasted eight hours. The volunteers lay on a couch in a living-room-like setting, wearing an eye mask and listening to classical music. They were encouraged to focus their attention inward.

Psilocybin's effects lasted for up to six hours, Griffiths said. Twenty-two of the 36 volunteers reported having a ''complete'' mystical experience, compared to four of those getting methylphenidate.

That experience included such things as a sense of pure awareness and a merging with ultimate reality, a transcendence of time and space, a feeling of sacredness or awe, and deeply felt positive mood like joy, peace and love. People say ''they can't possibly put it into words,'' Griffiths said.

Two months later, 24 of the participants filled out a questionnaire. Two-thirds called their reaction to psilocybin one of the five top most meaningful experiences of their lives. On another measure, one-third called it the most spiritually significant experience of their lives, with another 40 percent ranking it in the top five.

About 80 percent said that because of the psilocybin experience, they still had a sense of well-being or life satisfaction that was raised either ''moderately'' or ''very much.''

Scientific American Mind - December 28, 2007

Psychedelic Healing?

Hallucinogenic drugs, which blew minds in the 1960s, soon may be used to treat mental ailments

By David Jay Brown

Mind-altering psychedelics are back—but this time they are being explored in labs for their therapeutic applications rather than being used illegally. Studies are looking at these hallucinogens to treat a number of otherwise intractable psychiatric disorders, including chronic depression, post-traumatic stress disorder, and drug or alcohol dependency.

The past 15 years have seen a quiet resurgence of psychedelic drug research as scientists have come to recognize the long-underappreciated potential of these drugs. In the past few years, a growing number of studies using human volunteers have begun to explore the possible therapeutic benefits of drugs such as LSD, psilocybin, DMT, MDMA, ibogaine and ketamine.

Much remains unclear about the precise neural mechanisms governing how these drugs produce their mind-bending results, but they often produce somewhat similar psychoactive effects that make them potential therapeutic tools. Though still in their preliminary stages, studies in humans suggest that the day when people can schedule a psychedelic session with their therapist to overcome a serious psychiatric problem may not be that far off.

The Trip Begins
Psychedelic drug research began in 1897, when German chemist Arthur Heffter first isolated mescaline, the primary psychoactive compound in the peyote cactus. In 1943 Swiss chemist Albert Hofmann discovered the hallucinogenic effects of LSD (lysergic acid diethylamide) at Sandoz Pharmaceuticals in Basel while studying ergot, a fungus that grows on rye. Fifteen years later, in 1958, he was the first to isolate psilocybin and psilocin—the psychoactive components of the Mexican “magic mushroom,” Psilocybe mexicana.

Before 1972, close to 700 studies with psychedelic drugs took place. The research suggested that psychedelics offered significant benefits: they helped recovering alcoholics abstain, soothed the anxieties of terminal cancer patients, and eased the symptoms of many difficult-to-treat psychiatric illnesses, such as obsessive-compulsive disorder.

For example, between 1967 and 1972 studies in terminal cancer patients by psychiatrist Stanislav Grof and his colleagues at Spring Grove State Hospital in Baltimore showed that LSD combined with psychotherapy could alleviate symptoms of depression, tension, anxiety, sleep disturbances, psychological withdrawal and even severe physical pain. [A more recent replication of that finding is described here.] Other investigators during this era found that LSD may have some interesting potential as a means to facilitate creative problem solving.

Between 1972 and 1990 there were no human studies with psychedelic drugs. Their disappearance was the result of a political backlash that followed the promotion of these drugs by the 1960s counterculture. This reaction not only made these substances illegal for personal use but also made it extremely difficult for researchers to get government approval to study them.

Things began to change in 1990, when “open-minded regulators at the FDA decided to put science before politics when it came to psychedelic and medical marijuana research,” says Rick Doblin, a public policy expert and head of the Multidisciplinary Association for Psychedelic Studies (MAPS). “FDA openness to research is really the key factor. Also, senior researchers who were influenced by psychedelics in the sixties now are speaking up before they retire and have earned credibility.” Chemist and neuropharmacologist David E. Nichols of Purdue University adds, “Baby boomers who experienced the psychedelic sixties are now mature scientists and clinicians who have retained their curiosity but only recently had the opportunity to reexplore these substances.”

Research Begins Anew
The efforts of two privately funded organizations have catalyzed much of the recent wave of research: MAPS, founded in 1986 by Doblin, and the Heffter Research Institute, started in 1993. Outside the U.S. there are groups such as the Beckley Foundation in England and the Russian Psychedelic Society. These seek out interested researchers, assist in developing the experimental design for the studies, and help to obtain funding and government approval to conduct clinical trials. They have initiated numerous FDA-approved clinical trials in the U.S., Switzerland, Israel and Spain. So far the agency has approved seven studies, with two under review and more on the way.

Current studies are focusing on psychedelic treatments for cluster headaches, depression, obsessive-compulsive disorder (OCD), severe anxiety in terminal cancer patients, post-traumatic stress disorder (PTSD), alcoholism and opiate addiction. New drugs must pass three clinical milestones before they can be marketed to the public, called phase I (for safety, usually in 20 to 80 volunteers), phase II (for efficacy, in several hundred subjects) and phase III (more extensive data on safety and efficacy come from testing the drug in up to several thousand people). All the studies discussed in this article have received government approval, and their investigators are either in the process of recruiting human subjects or have begun or completed research on human subjects in the first or second stage of this trial process.

Psychedelic drugs affect all mental functions: perception, emotion, cognition, body awareness and one’s sense of self. Unlike every other class of drugs, psychedelic drug effects depend heavily on the environment and on the expectations of the subject, which is why combining them with psychotherapy is so vital.

“Psychedelics may be therapeutic to the extent that they elicit processes that are known to be useful in a therapeutic context: transference reactions and working through them; enhanced symbolism and imagery; increased suggestibility; increased contact between emotions and ideations; controlled regression; et cetera,” says psychiatrist Rick Strassman of the University of New Mexico School of Medicine, who from 1990 to 1995 performed the first human study using psychedelic drugs in about 20 years, investigating the effects of DMT on 60 human subjects. “This all depends, though, on set and setting,” he cautions. “These same properties could also be turned to very negative experiences, if the support and expectation for a beneficial experience aren’t there.”

Mechanisms and Targets
Scientists divide classical psychedelic drugs into two basic chemical groups: tryptamines (such as LSD, DMT and psilocybin) and phen­ethylamines (such as mescaline and MDMA). In addition, some people consider so-called dissociative anesthetics (such as ketamine and PCP) to be psychedelic drugs, although the way they affect the brain is quite different.

The exact mechanisms differ, but all the tryptamine hallucinogens—which make up the majority of psychedelic drugs—selectively bind to specific serotonin receptors on neurons, mimicking the effects of the nerve-signaling chemical, or neurotransmitter, serotonin on these receptors. Phenethylamines mimic the chemical structure of another neurotransmitter, dopamine. They actually bind to many of the same serotonin receptors activated by the tryptamines, however. Serotonin is responsible for many important functions, including mood, memory, appetite, sex and sleep. It is such an essential neurochemical that any substance—such as a hallucinogen—that interferes with its action might be expected to produce dramatic changes in brain function.

How do the drugs create their perceptual effects? Neuroscientists believe that activation of a particular set of serotonin receptors, the 2A subtype, which are highly expressed (or present) in the cortex, the outermost layer of the brain, interferes with the processing of sensory information. Consciousness is thought to involve a complex interaction among the cortex, the thalamus and the striatum. Disruption of this network by activation of serotonin 2A receptors is now the most popular theory for the mechanism of action for tryptamine and phenethylamine psychedelics.

“There are at least two possible mechanisms for beneficial actions,” Nichols says. “The first simply involves a change in the numbers of brain serotonin 2A receptors. Activation of serotonin 2A receptors by psychedelics causes the number of receptors expressed on the surface of neurons to decrease, a process called downregulation. For some disorders, such as OCD, it may be this receptor downregulation that could be therapeutic,” he explains. “The other possible mechanism is a psychological effect that is harder to define but in some way produces changes in the way the subject perceives pain and distress. Psychedelics seem able to produce a profound cognitive change that provides the patient with a new insight—the ability to see the world from a new perspective—somehow reducing anxiety and raising the pain threshold.”

MDMA (3,4-methylenedioxy-N-methylamphetamine) is also chemically classified as a phenethylamine, but its action in the brain is substantially different from that of other drugs discussed in this article. “In contrast to most psychedelics, MDMA does not directly stimulate serotonin 2A receptors but instead causes dopamine, serotonin and norepinephrine [another neurotransmitter] to be released from their stores in neuron endings,” Nichols says. There is some controversy about whether MDMA has neurotoxic effects. Most researchers believe, however, that the occasional moderate use of MDMA at therapeutic doses would not be damaging. There have been no recent studies using mescaline, although MAPS plans to initiate some in the future.

In contrast to the traditional psychedelics, the dissociative anesthetics selectively bind to N-methyl-D-aspartic acid (NMDA) receptors, block­ing the neurotransmitter glutamate from activating these receptors. “Because glutamate is an essential neurotransmitter that activates neurons, this blocking effect seems to prevent the processing of sensory information by the brain,” Nichols states.

Ketamine appears to hold particular promise as a psychedelic therapy because it is already among the selections in Western medicine’s pharmacopoeia. In addition to being part of a different chemical class of drugs than the other psychedelics, ketamine is in a separate legal class as an FDA-approved schedule III drug. This designation means that any physician can administer it for an off-label use if he or she believes it will help the patient.

Although some research indicates that psychedelic drugs may enhance suggestibility and certain aspects of psychotherapy, the benefits of dissociative anesthetics such as ketamine and ibogaine may simply be the result of enduring biochemical changes in the brain. For example, in 2006 Carlos Zarate of the National Institute of Mental Health published a study demon­strating ketamine’s unusual antidepressant properties. A single infusion of ketamine relieved symptoms of depression in some patients within a few hours, and that relief persisted for several days.

This was the third study that showed ketamine’s powerful and enduring antidepressant effects. In an intriguing finding from one of the previous studies, subjects received the ketamine as an anesthetic for orthopedic surgery—so they were not even conscious during the mind-altering segment of the drug’s action in the brain—and the antidepressant effects occurred postoperatively.

In other work seeking to help cure addicts, a preliminary ketamine study, in which psy­chiatrist Evgeny Krupitsky of St. Petersburg, Russia, treated 59 patients with heroin dependency, produced encouraging results. And the Iboga Therapy House in Vancouver, Canada, has recently begun a study that has so far successfully treated three out of 20 opiate-addicted subjects with ibogaine. The experimental procedure substantially reduced the withdrawal symptoms associated with opiate addiction, helping the addicts to recover and break their dependency on the drug.

OCD, Cluster Headaches and Cancer
In addition to the promising work with ibogaine and the dissociative anesthetics, progress is also being made in the study of conventional psychedelics. In 2006 investigators at the Johns Hopkins School of Medicine published the results of a six-year project on the effects of psilocybin, in which more than 60 percent of the participants reported positive changes in their attitude and behavior after taking the drug, a benefit that lasted for at least several months.

In another 2006 study, researchers at the University of Arizona, led by psychiatrist Francisco Moreno, found that psilocybin relieved the symptoms of nine patients with OCD. The patients suffered from a wide range of obsessions and compulsions. Some of them showered for hours; others put on their clothes over and over again until they felt right. All nine experienced improvements with at least some of the doses tested.

“What we saw was a drastic decrease in symp­toms for a period of time,” Moreno says. “People would report that it had been years since they had felt so good.” Moreno cautions that the goal

was simply to test the safety of administering psilocybin to OCD patients and that the true effectiveness of the drug is still in question until a larger controlled study can be conducted. Such a study is being planned, although there are currently no funds available for it. According to Moreno, however, no treatment in the medical literature eases OCD symptoms as fast as psilocybin does. Whereas other drugs take several weeks to show an effect, psilocybin worked almost immediately.

Preliminary results of a current study led by psychiatrist Charles Grob of the Harbor-UCLA Medical Center suggest that psilocybin may reduce the psychological distress associated with terminal cancer. This research seeks to measure the effectiveness of psilocybin on the reduction of anxiety, depression and physical pain in advanced-stage cancer patients. Grob’s study is almost complete; 11 out of 12 subjects have already been treated. Although the formal data analysis has not been completed, “my impression,” Grob says, “from just staying in touch with these people and following them is that some do seem to be functioning better psychologically. There seems to be less anxiety, improved mood and an overall improved quality of life. There also seems to be less fear of death.” [That study's results are described here.]

The first studies of psychedelic drugs at Harvard University since 1965 are also now under way. In one study, psychiatrist John Halpern and his colleagues are looking into using LSD and psilocybin to treat the debilitating symptoms of cluster headaches. The researchers, who are in the process of recruiting subjects, will probably begin trials in early 2008.

Acute Anxiety and PTSD
Another study at Harvard, also led by Halpern, will look into MDMA-assisted psychotherapy in subjects with anxiety associated with advanced-stage cancer—similar to Grob’s psilocybin study—using measures to evaluate anxiety, pain and overall quality of life. This study is also in the process of recruiting human subjects.

Psychiatrist Michael Mithoefer in Charleston, S.C., is running an MDMA study for treatment-resistant PTSD victims of crime, war or childhood sexual abuse. So far 17 out of 20 such subjects have already undergone the experimental therapy. “At this point the results are very promising,” Mithoefer says. “I think we’re seeing pretty strong, robust effects in some people. I hasten to add these are preliminary findings—we’re not ready to draw conclusions yet. But assuming it keeps going this way for the rest of the study, it certainly seems that there’s very good reason to go on to larger phase III trials.”

Although we are still in the early days of psychedelic therapy research, the initial data show considerable promise. A growing number of scientists believe that psychedelic drugs may offer safe and effective help for people with certain treatment-resistant psychiatric disorders and could possibly help some people who receive partial relief from current methods to obtain a more complete healing.

July 1, 2008

Study finds long benefit in illegal mushroom drug

By MALCOLM RITTER
AP Science Writer

In 2002, at a Johns Hopkins University laboratory, a business consultant named Dede Osborn took a psychedelic drug as part of a research project.

She felt like she was taking off. She saw colors. Then it felt like her heart was ripping open.

But she called the experience joyful as well as painful, and says that it has helped her to this day.

"I feel more centered in who I am and what I'm doing," said Osborn, now 66, of Providence, R.I. "I don't seem to have those self-doubts like I used to have. I feel much more grounded (and feel that) we are all connected."

Scientists reported Tuesday that when they surveyed volunteers 14 months after they took the drug, most said they were still feeling and behaving better because of the experience.

Two-thirds of them also said the drug had produced one of the five most spiritually significant experiences they'd ever had.

The drug, psilocybin, is found in so-called "magic mushrooms." It's illegal, but it has been used in religious ceremonies for centuries.

The study involved 36 men and women during an eight-hour lab visit. It's one of the few such studies of a hallucinogen in the past 40 years, since research was largely shut down after widespread recreational abuse of such drugs in the 1960s.

The project made headlines in 2006 when researchers published their report on how the volunteers felt just two months after taking the drug. The new study followed them up a year after that.

Experts emphasize that people should not try psilocybin on their own because it could be harmful. Even in the controlled setting of the laboratory, nearly a third of participants felt significant fear under the effects of the drug. Without proper supervision, someone could be harmed, researchers said.

Osborn, in a telephone interview, recalled a powerful feeling of being out of control during her lab experience. "It was ... like taking off, I'm being lifted up," she said. Then came "brilliant colors and beautiful patterns, just stunningly gorgeous, more intense than normal reality."

And then, the sensation that her heart was tearing open.

"It would come in waves," she recalled. "I found myself doing Lamaze-type breathing as the pain came on."

Yet "it was a joyful, ecstatic thing at the same time, like the joy of being alive," she said. She compared it to birthing pains. "There was this sense of relief and joy and ecstasy when my heart was opened."

With further research, psilocybin (pronounced SILL-oh-SY-bin) may prove useful in helping to treat alcoholism and drug dependence, and in aiding seriously ill patients as they deal with psychological distress, said study lead author Roland Griffiths of Johns Hopkins.

Griffiths also said that despite the spiritual characteristics reported for the drug experiences, the study says nothing about whether God exists.

"Is this God in a pill? Absolutely not," he said.

The experiment was funded in part by the National Institute on Drug Abuse. The results were published online Tuesday by the Journal of Psychopharmacology.

Fourteen months after taking the drug, 64 percent of the volunteers said they still felt at least a moderate increase in well-being or life satisfaction, in terms of things like feeling more creative, self-confident, flexible and optimistic. And 61 percent reported at least a moderate behavior change in what they considered positive ways.

That second question didn't ask for details, but elsewhere the questionnaire answers indicated lasting gains in traits like being more sensitive, tolerant, loving and compassionate.

Researchers didn't try to corroborate what the participants said about their own behavior. But in the earlier analysis at two months after the drug was given, researchers said family and friends backed up what those in the study said about behavior changes. Griffiths said he has no reason to doubt the answers at 14 months.

Dr. Charles Grob, a professor of psychiatry and pediatrics at the Harbor-UCLA Medical Center, called the new work an important follow-up to the first study.

He said it is helping to reopen formal study of psychedelic drugs. Grob is on the board of the Heffter Research Institute, which promotes studies of psychedelic substances and helped pay for the new work.

July 1, 2008

Long Trip: Magic Mushrooms' Transcendent Effect Lingers

Survey shows that profound mental changes induced by psilocybin have lasted for more than a year

By David Biello

People who took magic mushrooms were still feeling the love more than a year later, and one might say they were on cloud nine about it, scientists report in the Journal of Psychopharmacology.

"Most of the volunteers looked back on their experience up to 14 months later and rated it as the most, or one of the five most, personally meaningful and spiritually significant of their lives," comparing it with the birth of a child or the death of a parent, says neuroscientist Roland Griffiths of Johns Hopkins University School of Medicine, who led the research. "It's one thing to have a dramatic experience you say is impressive. It's another thing to say you consider it as meaningful 14 months later. There's something about the saliency of these experiences that's stunning."

Griffiths gave 36 specially screened volunteers psilocybin, the active ingredient in so-called magic mushrooms. The compound is believed to affect perception and cognition by acting on the same receptors in the brain that respond to serotonin, a neurotransmitting chemical tied to mood.

Afterward, about two thirds of the group reported having a "full mystical experience," characterized by a feeling of "oneness" with the universe. When Griffiths asked them how they were doing 14 months later, the same proportion gave the experience high marks for transcendental satisfaction, and credited it with increasing their well-being since then.

But some scientists noted that this psilocybin study was just the first trip on a long journey of understanding. "We don't know how far we can generalize these results," cautions neuroscientist Charles Schuster of Loyola University Chicago and a former director of the National Institute on Drug Abuse. "To attribute all of this to the drug, I think, is a mistake and to expect the same effects from simply taking the drug without this careful preparation in these kinds of people would be a mistake."

Herbert Kleber, who directs the division of substance abuse at Columbia University also notes that it is difficult to assess the mushroom's impact without detailed information on how individual lives were changed. For example, it remains unclear from the study whether volunteers really were more altruistic or simply claimed to be.

But the findings do seem to support reports of recreational users and what LSD guru and 1960s counterculture icon Timothy Leary made famous in his psychedelic lab at Harvard University.

Griffiths and Schuster are proponents of future research on psilocybin to determine whether it has long-term influence on the brain—and whether the reported mystical effects affect memory alone or stem from other physiological changes. This study is among the first of so-called "shrooms" in four decades, coming after the widespread, illegal use of hallucinogens as recreational drugs in the 1960s, which turned off corporate and academic researchers.

"I don't think the evidence is sufficiently strong for any beneficial effect in general for us to consider changing the legality of these substances until a great deal more research is done," Schuster says. "But the illegality should not interfere with this research."

For his part, Griffiths is now recruiting terminally illcancer patients for a trial that will test whether psilocybin mitigates the existential anxiety that comes with facing death. Strangely enough, he says, it may also be a salve for alcoholism and drug addiction.

"It does sound counterintuitive," Griffiths says. But, "six of the 12 AA [Alcoholics Anonymous] steps are related to a higher power and surrendering to it. Many people don't engage fully into the 12-step program because they don't have a connection to a higher power. One can't help but wonder whether an experience like this might be useful."

April 11, 2010

Hallucinogens Have Doctors Tuning In Again

By JOHN TIERNEY

As a retired clinical psychologist, Clark Martin was well acquainted with traditional treatments for depression, but his own case seemed untreatable as he struggled through chemotherapy and other grueling regimens for kidney cancer. Counseling seemed futile to him. So did the antidepressant pills he tried.

Nothing had any lasting effect until, at the age of 65, he had his first psychedelic experience. He left his home in Vancouver, Wash., to take part in an experiment at Johns Hopkins medical school involving psilocybin, the psychoactive ingredient found in certain mushrooms.

Scientists are taking a new look at hallucinogens, which became taboo among regulators after enthusiasts like Timothy Leary promoted them in the 1960s with the slogan “Turn on, tune in, drop out.” Now, using rigorous protocols and safeguards, scientists have won permission to study once again the drugs’ potential for treating mental problems and illuminating the nature of consciousness.

After taking the hallucinogen, Dr. Martin put on an eye mask and headphones, and lay on a couch listening to classical music as he contemplated the universe.

“All of a sudden, everything familiar started evaporating,” he recalled. “Imagine you fall off a boat out in the open ocean, and you turn around, and the boat is gone. And then the water’s gone. And then you’re gone.”

Today, more than a year later, Dr. Martin credits that six-hour experience with helping him overcome his depression and profoundly transforming his relationships with his daughter and friends. He ranks it among the most meaningful events of his life, which makes him a fairly typical member of a growing club of experimental subjects.

Researchers from around the world are gathering this week in San Jose, Calif., for the largest conference on psychedelic science held in the United States in four decades. They plan to discuss studies of psilocybin and other psychedelics for treating depression in cancer patients, obsessive-compulsive disorder, end-of-life anxiety, post-traumatic stress disorder and addiction to drugs or alcohol.

The results so far are encouraging but also preliminary, and researchers caution against reading too much into these small-scale studies. They do not want to repeat the mistakes of the 1960s, when some scientists-turned-evangelists exaggerated their understanding of the drugs’ risks and benefits.

Because reactions to hallucinogens can vary so much depending on the setting, experimenters and review boards have developed guidelines to set up a comfortable environment with expert monitors in the room to deal with adverse reactions. They have established standard protocols so that the drugs’ effects can be gauged more accurately, and they have also directly observed the drugs’ effects by scanning the brains of people under the influence of hallucinogens.

Scientists are especially intrigued by the similarities between hallucinogenic experiences and the life-changing revelations reported throughout history by religious mystics and those who meditate. These similarities have been identified in neural imaging studies conducted by Swiss researchers and in experiments led by Roland Griffiths, a professor of behavioral biology at Johns Hopkins.

In one of Dr. Griffiths’s first studies, involving 36 people with no serious physical or emotional problems, he and colleagues found that psilocybin could induce what the experimental subjects described as a profound spiritual experience with lasting positive effects for most of them. None had had any previous experience with hallucinogens, and none were even sure what drug was being administered.

To make the experiment double-blind, neither the subjects nor the two experts monitoring them knew whether the subjects were receiving a placebo, psilocybin or another drug like Ritalin, nicotine, caffeine or an amphetamine. Although veterans of the ’60s psychedelic culture may have a hard time believing it, Dr. Griffiths said that even the monitors sometimes could not tell from the reactions whether the person had taken psilocybin or Ritalin.

The monitors sometimes had to console people through periods of anxiety, Dr. Griffiths said, but these were generally short-lived, and none of the people reported any serious negative effects. In a survey conducted two months later, the people who received psilocybin reported significantly more improvements in their general feelings and behavior than did the members of the control group.

The findings were repeated in another follow-up survey, taken 14 months after the experiment. At that point most of the psilocybin subjects once again expressed more satisfaction with their lives and rated the experience as one of the five most meaningful events of their lives.

Since that study, which was published in 2008, Dr. Griffiths and his colleagues have gone on to give psilocybin to people dealing with cancer and depression, like Dr. Martin, the retired psychologist from Vancouver. Dr. Martin’s experience is fairly typical, Dr. Griffiths said: an improved outlook on life after an experience in which the boundaries between the self and others disappear.

In interviews, Dr. Martin and other subjects described their egos and bodies vanishing as they felt part of some larger state of consciousness in which their personal worries and insecurities vanished. They found themselves reviewing past relationships with lovers and relatives with a new sense of empathy.

“It was a whole personality shift for me,” Dr. Martin said. “I wasn’t any longer attached to my performance and trying to control things. I could see that the really good things in life will happen if you just show up and share your natural enthusiasms with people. You have a feeling of attunement with other people.”

The subjects’ reports mirrored so closely the accounts of religious mystical experiences, Dr. Griffiths said, that it seems likely the human brain is wired to undergo these “unitive” experiences, perhaps because of some evolutionary advantage.

“This feeling that we’re all in it together may have benefited communities by encouraging reciprocal generosity,” Dr. Griffiths said. “On the other hand, universal love isn’t always adaptive, either.”

The work has been supported by nonprofit groups like the Heffter Research Institute and MAPS, the Multidisciplinary Association for Psychedelic Studies.

“There’s this coming together of science and spirituality,” said Rick Doblin, the executive director of MAPS. “We’re hoping that the mainstream and the psychedelic community can meet in the middle and avoid another culture war. Thanks to changes over the last 40 years in the social acceptance of the hospice movement and yoga and meditation, our culture is much more receptive now, and we’re showing that these drugs can provide benefits that current treatments can’t.”

Researchers are reporting preliminary success in using psilocybin to ease the anxiety of patients with terminal illnesses. Dr. Charles S. Grob, a psychiatrist who is involved in an experiment at U.C.L.A., describes it as “existential medicine” that helps dying people overcome fear, panic and depression.

“Under the influences of hallucinogens,” Dr. Grob writes, “individuals transcend their primary identification with their bodies and experience ego-free states before the time of their actual physical demise, and return with a new perspective and profound acceptance of the life constant: change.”

April 20, 2012

How Psychedelic Drugs Can Help Patients Face Death

Pam Sakuda was 55 when she found out she was dying. Shortly after having a tumor removed from her colon, she heard the doctor’s dreaded words: Stage 4; metastatic. Sakuda was given 6 to 14 months to live. Determined to slow her disease’s insidious course, she ran several miles every day, even during her grueling treatment regimens. By nature upbeat, articulate and dignified, Sakuda — who died in November 2006, outlasting everyone’s expectations by living for four years — was alarmed when anxiety and depression came to claim her after she passed the 14-month mark, her days darkening as she grew closer to her biological demise. Norbert Litzinger, Sakuda’s husband, explained it this way: “When you pass your own death sentence by, you start to wonder: When? When? It got to the point where we couldn’t make even the most mundane plans, because we didn’t know if Pam would still be alive at that time — a concert, dinner with friends; would she still be here for that?” When came to claim the couple’s life completely, their anxiety building as they waited for the final day.

As her fears intensified, Sakuda learned of a study being conducted by Charles Grob, a psychiatrist and researcher at Harbor-U.C.L.A. Medical Center who was administering psilocybin — an active component of magic mushrooms — to end-stage cancer patients to see if it could reduce their fear of death. Twenty-two months before she died, Sakuda became one of Grob’s 12 subjects. When the research was completed in 2008 — (and published in the Archives of General Psychiatry last year) — the results showed that administering psilocybin to terminally ill subjects could be done safely while reducing the subjects’ anxiety and depression about their impending deaths.

Grob’s interest in the power of psychedelics to mitigate mortality’s sting is not just the obsession of one lone researcher. Dr. John Halpern, head of the Laboratory for Integrative Psychiatry at McLean Hospital in Belmont Mass., a psychiatric training hospital for Harvard Medical School, used MDMA — also known as ecstasy — in an effort to ease end-of-life anxieties in two patients with Stage 4 cancer. And there are two ongoing studies using psilocybin with terminal patients, one at New York University’s medical school, led by Stephen Ross, and another at Johns Hopkins Bayview Medical Center, where Roland Griffiths has administered psilocybin to 22 cancer patients and is aiming for a sample size of 44. “This research is in its very early stages,” Grob told me earlier this month, “but we’re getting consistently good results.”

Grob and his colleagues are part of a resurgence of scientific interest in the healing power of psychedelics. Michael Mithoefer, for instance, has shown that MDMA is an effective treatment for severe P.T.S.D. Halpern has examined case studies of people with cluster headaches who took LSD and reported their symptoms greatly diminished. And psychedelics have been recently examined as treatment for alcoholism and other addictions.

Despite the promise of these investigations, Grob and other end-of-life researchers are careful about the image they cultivate, distancing themselves as much as possible from the 1960s, when psychedelics were embraced by many and used in a host of controversial studies, most famously the psilocybin project run by Timothy Leary. Grob described the rampant drug use that characterized the ’60s as “out of control” and said of his and others’ current research, “We are trying to stay under the radar. We want to be anti-Leary.” Halpern agreed. “We are serious sober scientists,” he told me.

Sakuda’s terminal diagnosis, combined with her otherwise perfect health, made her an ideal subject for Grob’s study. Beginning in January 2005, Grob and his research team gave Sakuda various psychological tests, including the Beck Depression Inventory and the Stai-Y anxiety scale to establish baseline measures of Sakuda’s psychological state and to rule out any severe psychiatric illness. “We wanted psychologically healthy people,” Grob says, “people whose depressions and anxieties are not the result of mental illness” but rather, he explained, a response to a devastating disease.

Sakuda would take part in two sessions, one with psilocybin, one with niacin, an active placebo that can cause some flushing in the face. The study was double blind, which meant that neither the researchers nor the subjects knew what was in the capsules being administered. On the day of her first session, Sakuda was led into a room that researchers had transformed with flowing fabrics and fresh flowers to help create a soothing environment in an otherwise cold hospital setting. Sakuda swallowed a capsule and lay back on the bed to wait. Grob had invited her — as researchers do with all their subjects — to bring objects from home that had special significance. “These objects often personalize the session room for the volunteer and often prompt the patient to think about loved ones or important life events,” Roland Griffiths, of Johns Hopkins, says.

“I think it’s kind of goofy,” Halpern says, “but the thinking is that with the aid of the psychedelic, you may come to see the object in a different light. It may help bring back memories; it promotes introspection, it can be a touchstone, it can be grounding.”

Sakuda brought a few pictures of loved ones, which, Grob recalled, she clutched in her hands as she lay back on the bed. By her side were Grob and one of his research assistants, both of whom stayed with the subjects for the six-to-seven-hour treatment session. Sakuda knew that there would be time set aside in the days and weeks following when she would meet with Grob and his team to process what would happen in that room. Black eyeshades were draped over Sakuda’s face, encouraging her to look inward. She was given headphones. Music was piped in: the sounds of rivers rushing, sweet staccatos, deep drumming. Each hour, Grob and his staff checked in with Sakuda, as they did with every subject, asking if all was O.K. and taking her blood pressure. At one point, Grob observed that Sakuda, with the eyeshades draped over her face, began to cry. Later on, Sakuda would reveal to Grob that the source of her tears was a keen empathetic understanding of what her spouse Norbert would feel when she died.

Grob’s setup — the eyeshades, the objects, the mystical music, the floral aromas and flowing fabrics — was drawn from the work of Stanislav Grof, a psychiatrist born in Prague and a father of the study of psychedelic medicine for the dying. In the mid-’60s — before words like “acid” and “bong” and “Deadhead” transformed the American landscape, at a time when psychedelics were not illegal because most people didn’t know what they were and thus had no urge to ingest them — Grof began giving the drug to cancer patients at the Spring Grove State Hospital near Baltimore and documenting their effects.

Grof kept careful notes of his many psychedelic sessions, and in his various papers and books derived from those sessions, he described cancer patients clenched with fear who, under the influence of LSD or DPT, experienced relief from the terror of dying — and not just during their psychedelic sessions but for weeks and months afterward. Grof continued his investigations into psychedelics for the dying until the culture caught up with him — the recreational use of drugs and the reaction against them leading to harsh antidrug laws. (Richard Nixon famously called Timothy Leary “the most dangerous man in America.”) Financing for psychedelic studies dried up, and Grof turned his attention to developing alternative methods of accessing higher states of consciousness. It is only now, decades later, that Grob and a handful of his fellow scientists feel they can re-examine Grof’s methods and outcomes without risking their reputations.

Norbert Litzinger remembers picking up his wife from the medical center after her first session and seeing that this deeply distressed woman was now “glowing from the inside out.” Before Pam Sakuda died, she described her psilocybin experience on video: “I felt this lump of emotions welling up . . . almost like an entity,” Sakuda said, as she spoke straight into the camera. “I started to cry. . . . Everything was concentrated and came welling up and then . . . it started to dissipate, and I started to look at it differently. . . . I began to realize that all of this negative fear and guilt was such a hindrance . . . to making the most of and enjoying the healthy time that I’m having.” Sakuda went on to explain that, under the influence of the psilocybin, she came to a very visceral understanding that there was a present, a now, and that it was hers to have.

Two weeks after Sakuda’s psilocybin session, Grob readministered the depression and anxiety assessments. Over all among his subjects, he found that their scores on the anxiety scale at one and three months after treatment “demonstrated a sustained reduction in anxiety,” the researchers wrote in The Archives of General Psychiatry. They also found that their subjects’ scores on the Beck Depression Inventory dropped significantly at the six-month follow-up. “The dose of psilocybin that we gave our subjects was relatively low in comparison to the doses in Stanislav Grof’s studies,” Grob told me. “Nevertheless, and even with this modest dose, it appears the drug can relieve the angst and fear of the dying.”

Lauri Reamer is a 48-year-old survivor of adult-onset leukemia. Before the leukemia, she was an anesthesiologist and a committed agnostic who believed in “validity” and “reliability,” the scientific method her route to truth. Reamer recalls the morning when all that changed, when, utterly depleted, she bumped her leg on a railing and saw a bruise rush up, livid on her pale flesh; it was then she knew something was terribly wrong. After that came the diagnosis, the bone-marrow biopsies, the terrible trek toward a recovery that was tentative at best. “I believed I was going to die,” Reamer told me.

Reamer made it through the leukemia — or, rather, she went into remission — but the illness and the brutal bone-marrow treatments she underwent left a deep mental scar, a profound fear that the cancer would return made it difficult to experience any joy in life. Her illness was lurking around every corner, waiting to haul her away. “When I was near death, I wasn’t so afraid of it,” Reamer said, “but once I went into remission, well, I had an intense fear and anxiety around relapse and death.”

It was in the midst of this fear that, one day in May 2010, Reamer learned about Griffiths’s study at Johns Hopkins. For years, Griffiths had been studying the effects of psilocybin on healthy volunteers. He wanted to see if particular doses of the drug could induce mystical states similar to naturally occurring ones: think Joan of Arc or Paul on the road to Damascus. Griffiths says that he and his research team found an ideal range of dosage levels — 20 to 30 milligrams of psilocybin — that not only reliably stimulated “mystical insights” but also elicited “sustained positive changes in attitude, mood and behavior” in the study volunteers. Specifically, when Griffiths administered a psychological test called the Death Transcendance Scale at the 1- and 14-month follow-up, he saw subjects’ ratings rise on statements like “Death is never just an ending but part of a process” and “My death does not end my personal existence.”

“After transcendent experiences, people often have much less fear of death,” Griffiths says. Fourteen months after participating in a psilocybin study that was published in The Journal of Psychopharmacology last year, 94 percent of subjects said that it was one of the five most meaningful experiences of their lives; 39 percent said that it was the most meaningful experience.

Wondering whether he could see the same shifts in attitude in terminally ill patients, he designed a study that gave subjects a high dose of psilocybin (higher than Grob had given) in one session and a dose that varied from subject to subject in a second session. Because the study is continuing, Griffiths did not want to discuss the precise amounts of the drug given, but said that “dose selection in the cancer study is informed by what we have learned in the prior studies.”

At the end of September 2010, Lauri Reamer took her first dose of psilocybin. “I mostly just cried through that session,” she says. Three weeks later, she went back to Johns Hopkins for her second dose. She remembers a lovely room with a large plush couch. Griffiths entered and wished her well. Reamer had pictures of her children and items that reminded her of her recently deceased father, and after swallowing the psilocybin capsule, Reamer sat with two study coordinators and looked at the memorabilia. She talked about what each item meant to her, waiting for the drug to take effect, assessing her own internal state. “And then it happened,” she told me. “I was at first sitting up on the couch and talking about my daughter’s baby blanket, which I’d brought with me, and then I went supine. They dimmed the lights. I got dark eyeshades. They put headphones on me, and music started pouring into my ears. Some dark opera. Some choral music. Some mystical music. There was a bowl of grapes; they were big juicy grapes,” Reamer says, and she remembers the sweetness, the freshness, the tiny seeds embedded in the gel.

Once the drug took effect, Reamer lay there and rode the music’s dips and peaks. Reamer said that her mind became like a series of rooms, and she could go in and out of these rooms with remarkable ease. In one room there was the grief her father experienced when Reamer got leukemia. In another, her mother’s grief, and in another, her children’s. In yet another room was her father’s perspective on raising her. “I was able to see things through his eyes and through my mother’s eyes and through my children’s eyes; I was able to see what it had been like for them when I was so sick.”

Reamer took the psilocybin at about 9 a.m., and its effects lasted until about 4 p.m. That night at home, she slept better than she had in a long time. The darkness finally stopped scaring her, and she was willing to go under, not because she knew she would come back up but because “under” was not as frightening. Why she was less afraid to die is hard for her to explain. “I now have the distinct sense that there’s so much more,” she says, “so many different states of being. I have the sense that death is not the end but just part of a process, a way of moving into a different sphere, a different way of being.”

After Reamer’s psilocybin experience, she separated from her husband. Eventually, she stopped practicing medicine. She started regularly meditating. She bought a house. “I read somewhere that, with my kind of leukemia, even if I stay in remission, the most I have left is 15 or 20 years. So that’s my sentence. But after I die, well, there could be a next phase. I believe that now.”

Researchers acknowledge that it’s not clear how psilocybin reduces a person’s anxiety about mortality, not simply during the trip but for weeks and months following. “It’s a bit of a mystery,” Grob says. “I don’t really have altogether a definitive answer as to why the drug eases the fear of death, but we do know that from time immemorial individuals who have transformative spiritual experiences come to a very different view of themselves and the world around them and thus are able to handle their own deaths differently.”

“On psychedelics,” Halpern says, “you have an experience in which you feel there is something you are a part of, something else is out there that’s bigger than you, that there is a dazzling unity you belong to, that love is possible and all these realizations are imbued with deep meaning. I’m telling you that you’re not going to forget that six months from now. The experience gives you, just when you’re on the edge of death, hope for something more.”

If psilocybin can so reliably induce these life-altering experiences, why have the hundreds of thousands of Americans who have taken magic mushrooms recreationally not had this profound experience? Grob explains that in addition to the carefully controlled setting of these studies and the opportunity to process the experience with the researchers, the subjects are primed for transcendence before they even take the drug. “Unlike the recreational user, we process the experience ahead of time,” Grob says. “We make it very clear up front that the hoped-for outcome is therapeutic, that they’ll have less anxiety, less depression and a greater acceptance of death.” Subjects, in other words, intend to have a transformative experience. Grob says that psilocybin taken in this setting is “existential medicine.”

For all the eloquence of these explanations, however, something feels fuzzy about a phenomenon in which a cancer-ridden patient takes a pill and overcomes her fear of death not just for the moment but for weeks and months that follow. A recent British study, published in The Proceedings of the National Academy of Sciences earlier this year, may begin to help us understand what might be happening here. In this study, David J. Nutt, a psychiatrist at the Imperial College London, and his team used an M.R.I. to scan healthy volunteers dosed on psilocybin in order to “capture the transition from normal waking consciousness to the psychedelic state.” The researchers found that the states of “unrestrained consciousness” that accompany the ingestion of psilocybin are associated with a deactivation of regions of the brain that integrate our senses and our perception of self. In depressed people, Nutt explains, one of those regions, the anterior cingulate cortex, is overactive, and psilocybin may work to shut it down. Nutt is planning a study in which he will give psilocybin to individuals with treatment resistant depression and see whether the drug can ease some of depression’s most recalcitrant symptoms.

Perhaps end-stage cancer patients are able to capture enduring benefits of psilocybin precisely because they are processing their drug experiences again and again with research staff and in doing so are changing the way the brain encodes positive memories. The phenomenon might be similar to how other memories work; when we remember something sweet-smelling, the olfactory neurons in our brain start to stir; when we remember running, our motor cortex begins to buzz. If this is the case then merely recalling the trip could resurrect its neural correlates, allowing the person to re-experience the insight, the awareness, the hope.

Because Grob and other psychedelic researchers are careful to separate their scientific work from the shadow of the 1960s, they have a complicated relationship with a psychedelic advocate named Rick Doblin, the founder and executive director of the Multidisciplinary Association for Psychedelic Study (MAPS), located in Santa Cruz, Calif. Doblin is not a psychiatrist — his advanced degree in public policy is from Harvard’s Kennedy School — and his mission is to legalize psychedelics so they can be prescribed for “a wide range of clinical indications.” Doblin says, in addition, “these substances should be available for things that are not diseases, like personal growth, spirituality, couples’ counseling.”

Despite their differing stances, MAPS and researchers meet at many points. Doblin, for instance, has F.D.A. approval to do a study on the psychological effects of MDMA when taken by healthy volunteers. His subjects will be therapists who are taking part in a MAPS program that teaches them how to guide their clients through psychedelic journeys. Doblin also worked closely with the Swiss researcher Dr. Peter Gasser in investigating the safety and efficacy of LSD-assisted psychotherapy for subjects with anxiety stemming from life-threatening illnesses.

“Rick Doblin has done a lot for the field, but he is more of a populist,” Grob says. “We need careful and controlled scientific studies showing the efficacy of these drugs so funding can continue.” Broader awareness of these sorts of end-of-life psychedelic studies could be good for everyone, the researchers say. “If insurance companies knew about our outcomes, they might get a lot more interested in what we’re doing here.” Griffiths continued: “When you make people less afraid to die, then they’re less likely to cling to life at a huge cost to society. After having such a transcendent experience, individuals with terminal illness often show a markedly reduced fear of dying and no longer feel the need to aggressively pursue every last medical intervention available. Instead they become more interested in the quality of their remaining life as well as the quality of their death.”

In a future still far off, Grob imagines retreat centers where the dying could have psilocybin administered to them by a staff trained for the task. Doblin asks: “Why confine this to just the dying? This powerful intervention could be used with young adults who could then reap the benefits of it much earlier.” The subjects who have undergone psilocybin treatment report an increased appreciation for the time they have left, a deeper awareness of their roles in the cycle of life and an increased motivation to invest their days with meaning. “Imagine allowing young adults, who have their whole lives in front of them, access to this kind of therapy,” Doblin says. “Imagine the kind of lives they could then create.”

If David Nutt, in Britain, is able to prove the efficacy of psilocybin for treatment-resistant depression, would the F.D.A. ever consider approving it for that use? And if that ever were to happen, what sort of slippery slope would we find ourselves on? If, say, end-stage cancer patients can have it, then why not all individuals over the age of, say, 75? If treatment-resistant depressives can have it, then why not their dysthymic counterparts, who suffer in a lower key but whose lives are clearly compromised by their chronic pain? And if dysthymic individuals can have it, then why not those suffering from agoraphobia, shut up day and night in cramped quarters, Xanax bottles littered everywhere?

Halpern is not particularly worried about this theoretical future, in large part because he doesn’t see much hope for psilocybin as a medicine. “There’s no money in it,” he says. “What drug company is going to invest millions in a substance widely available in our flora and fauna?” Grob has a more practical response, suggesting that, in our theoretical future, drugs like psilocybin should be reserved for only those who have no other alternatives. “There’s a lot of good treatment for depression,” he says. “And anxiety too. A drug like psilocybin, or maybe psilocybin itself, should be reserved for those who have no other treatment options.”

Besides, Grob told me, scientists are still at the very early stages of this research. “Twelve people,” he says of the size of his study. “One study with 12 people is not very definitive.” And yet, talking to him, you can hear a hint of excitement, something rising. “We saw remarkable and sustained changes in cancer patients’ spiritual dispositions. People’s entire sense of who they are has been altered in a positive manner.” He is looking forward to the day, he told me, when Griffiths and Ross “crunch their numbers” from their current studies. Grob says, “From what they say they’re seeing, it all sounds very positive.” Perhaps, then, we need not understand precisely how and why psilocybin works, accepting, as Halpern puts it, that “when you combine the chemical, the corporeal and the spiritual, you get a spark. You get magic.”

I have been working with junkies all my adult life. I have met them all and know all the stories. Usually people turn to hallucinogenic substances when they are depressed, poor, alone or because they are stupid. I believe that things should be tried once. Drugs should never be tried because in 25% of the cases this trying thing ends in a drug rehab clinic and a very bad case of detoxing. I've met the ones that say they use whatever they can to get closer to God. I think that's just a trick their mind plays on them. But how do you make them realize this or accept it when they believe they are the chosen ones?

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